Global surveillance as an antimicrobial stewardship strategy: Updates from ASM Microbe 2018

Issue: August 2018

ByGeorge G. Zhanel, PhD PharmD

Antimicrobial stewardship efforts and infection control and prevention begin with surveillance. ASM Microbe 2018 featured updates from several major, global surveillance studies. As reported by SENTRY, the Canadian Ward Surveillance (CANWARD) study and Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS), the gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae were among the most common pathogens collected at medical centers worldwide, across eight Canadian provinces, in United States ICUs, and among hematology-oncology patients in Europe.

Surveillance helps hospitals, states, regions and countries track trends in antimicrobial resistance. A SENTRY poster by Deshpande and colleagues reported that the global prevalence of nonsusceptible Enterobacteriaceae increased from 1.5% of isolates collected from 2007 to 2009 to 2.7% of isolates collected from 2014 to 2016, and that the prevalence of K. pneumoniae among these isolates increased from 77.4% to 84.4%. In a symposium talk summarizing recent SENTRY data, Mariana Castanheira, PhD, noted a rise in multidrug-resistant (MDR) pathogens, from 2.7% to 9.7%, and a SENTRY poster by Diekema and colleagues reported a steady increase over 20 years in the proportion of MDR Enterobacteriaceae — from 6.2% to 15.8% — with the highest prevalence seen in Latin America and among hospital-onset infections. Diekema and colleagues also reported that MDR frequency was highest among A. baumannii (70.6%) and P. aeruginosa (26.3%), and that 0.9% of A. baumannii and approximately 0.1% of P. aeruginosa are now pan-drug resistant. A CANWARD poster by Golden and colleagues reported MDR frequencies of 15% among P. aeruginosa, 26.3% among E. coli and 8.6% among K. pneumoniae, and extremely drug resistant (XDR) frequencies of 14.9% among E. coli, 5.4% of K. pneumoniae, and 2% of P. aeruginosa isolates collected in Canada. Golden and colleagues also reported that the proportion of MDR and XDR E. coli and K. pneumoniae increased significantly from 2007 through 2016. Sader and colleagues reported INFORM data on MDR and XDR frequencies stratified by U.S. geographic regions, as defined by the U.S. Census Bureau. The study showed that, in 2017, the proportion of MDR P. aeruginosa ranged from 18.6% in the East South Central region to 32.7% in the West South Central region, and the proportion of XDR P. aeruginosa ranged from 6.8% in the South Atlantic region to 19.9% in the West South Central region.

These studies also tracked trends in specific resistance mechanisms. Both CANWARD and SENTRY reported significant increases in extended-spectrum beta-lactamase (ESBL)-producing E. coli over an 11- to 20-year period. CANWARD also reported that ESBL-producing E. coli accounted for a substantial proportion of E. coli isolated from ICUs. SENTRY data tracked an increase in carbapenem-resistant Enterobacteriaceae (CRE), driven primarily by a rise in resistant K. pneumoniae. The incidence of carbapenemase production among CRE increased from 76.7% of isolates collected by SENTRY from 2007 to 2009 to 95.6% of those collected from 2014 to 2016, with the most prominent carbapenemase gene being blaKPC and the incidence of blaNDM expanding globally from 2.9% in India to 11.5% worldwide.

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Surveillance helps hospitals not only to track how pathogens are changing and spreading, but also to benchmark themselves against similar-sized institutions and focus their infection control and prevention as well as their antimicrobial stewardship efforts. Yet knowing what is happening in the hospital overall is not enough. Hospitals are also using surveillance data to monitor what is happening in various hospital wards. Traditional teaching states that antimicrobial resistance is highest in ICUs, followed by medical and surgical wards and emergency rooms (ERs), and that resistance also differs between pediatric and adult patients. At ASM Microbe 2018, however, a CANWARD poster reported that most pathogens were collected from medical wards (30.1%), followed by the ER (24.6%) and the ICU (18.8%) or clinic (18.2%).

Surveillance is also helping us track the activity of antimicrobials targeting gram-negative pathogens. Ceftolozane-tazobactam (C/T) continues to be the most potent antimicrobial against P. aeruginosa, as reported by CANWARD, PACTS and INFORM. CANWARD reported C/T MIC50 of 1 and MIC90 of 8 µg/mL vs. P. aeruginosa, and SMART, PACTS and INFORM reported overall C/T susceptibility rates exceeding 90%. PACTS reported high C/T susceptibility rates against resistant P. aeruginosa phenotypes, including MDR isolates (74.3%) and those nonsusceptible to colistin (75.0%), levofloxacin (77.1%), meropenem (75.4%) and piperacillin-tazobactam (73.7%). INFORM, on the other hand, reported C/T susceptibility rates of 91.4% against MDR P. aeruginosa isolates and 83.2% against XDR isolates. As reported by PACTS, C/T was the only beta-lactam with susceptibility rates higher than 90% against P. aeruginosa, E. coli and K. pneumoniae in ICUs across the U.S. With respect to ceftazidime-avibactam (C/A), CANWARD reported that the addition of avibactam to ceftazidime reduced MIC50 to a range of less than 0.06 to 1 µg/mL and MIC90 to a range of 0.12 to 16 ug/mL for all organisms collected, except for A. baumannii and Stenotrophomonas maltophilia. CANWARD reported C/A susceptibility rates higher than 70% against P. aeruginosa isolates that were resistant to ceftazidime, meropenem or piperacillin-tazobactam. CANWARD and INFORM also reported C/A susceptibility rates exceeding 99% against all Enterobacteriaceae in Canada and Latin America. In Latin America, isolates included those nonsusceptible to meropenem and non-metallo-beta-lactamase-producing isolates that were nonsusceptible to colistin.

Surveillance studies are also tracking antimicrobials that have not yet reached the market. Several ASM Microbe 2018 posters presented surveillance data on imipenem-relebactam (I/R). The CANWARD study reported high I/R activity against common Enterobacteriaceae collected in 2016 and 2017, with MIC90s of 0.25 µg/mL against E. coli and ESBL-producing E. coli and 0.5 µg/mL against K. pneumoniae. I/R also showed activity against two K. pneumoniae carbapenemase (KPC)-producing E. coli isolates and against P. aeruginosa (MIC90 2 µg/mL). SMART posters by Lob and colleagues reported I/R susceptibility rates exceeding 89% against P. aeruginosa in the U.S. and Europe, 80.5% against MDR P. aeruginosa in the U.S., and 68.7% against MDR P. aeruginosa in Europe. SMART also reported I/R susceptibility rates exceeding 96% against Enterobacteriaceae and 92.9% against KPC-producing Enterobacteriaceae in the U.S. and Europe. Lob reported that I/R was active against MDR isolates of P. aeruginosa and Enterobacteriaceae, including strains resistant to three to five different antimicrobial classes.

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An enormous gap remains in surveillance among community practices, even as most antibiotics used in the U.S. — about 80% — are used in these settings. Community practices send their specimens to private laboratories, who frequently do not participate in surveillance studies. Hospital-based stewardship programs have reached out to community practices, but surveillance often is not discussed. As a result, it is difficult to determine whether an infection was acquired in the community, and limited data are available on community resistance patterns. However, the hospital-based surveillance data we have could guide antimicrobial stewardship and infection control and prevention efforts in the community. For example, CANWARD researchers have presented community practices with ER surveillance data, which is closest to representing what happens in the community.

The scope of surveillance as a foundation for antimicrobial stewardship is beginning to expand beyond medical practice as part of increasing discussions of “One Health,” or the notion that pathogens and potential infections arise from interactions between humans and their environment. As recently as 5 years ago, conferences such as ASM Microbe did not mention One Health, and the discussions of farm animals were part of another world. Yet, ASM Microbe 2018 included poster presentations on the occurrence of ESBL-producing E. coli among MDR Enterobacteriaceae collected from sheep, dramatic increases in fluoroquinolone resistance among E. coli isolates collected from swine, and the persistence of ESBL-producing E. coli in the poultry production chain. Whereas once each silo would blame others for emerging antibiotic resistance, the One Health perspective is promoting a more collaborative approach to address the problem.

Discussions between microbiologists and veterinarians in Canada often begin with a presentation of CANWARD data, followed by animal data showing that these can be the same organisms with the same resistance patterns. This type of surveillance data lends credibility to our suggestions on changes in veterinary practice. Further collaboration with more specialists, family doctors, community practitioners, generalists, veterinarians and agricultural researchers at conferences such as ASM Microbe can expand the reach of surveillance data in driving antimicrobial stewardship.

References:
Castanheira M. Antimicrobial surveillance: recent results from the SENTRY program. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Deshpande L, et al. Abstract 6546. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Diekema D, et al. Abstract 4851. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Estabrook M, et al. Abstract 3491. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Golden A, et al. Abstract 2345. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Herault H, et al. Abstract 5356. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Hayer S, et al. Abstract 5463. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Lagacé-Wiens P, et al. Abstract 3525. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Lob S, et al. Abstract 4368. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Lob S, et al. Abstract 4377. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Lob S, et al. Abstract 4392. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Lob S, et al. Abstract 4449. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Lob S, et al. Abstract 4455. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Palmeira J, et al. Abstract 4246. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Sader H, et al. Abstract 4403. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Shortridge D, et al. Abstract 4296. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Shortridge D, et al. Abstract 4298. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Shortridge D, et al. Abstract 4841. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Wang Z, et al. Abstract 7117. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Zhanel G, et al. Abstract 4596. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Zhanel G, et al. Abstract 4601. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.
Zhanel G, et al. Abstract 4951. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.

For more information:
George G. Zhanel, PhD, PharmD, is a professor in the department of medical microbiology and infectious diseases at the Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba. He is also the director of the Canadian Antimicrobial Resistance Alliance.

Disclosure: Zhanel reports receiving research grants from Abbott, Achaogen, Affinium, Astellas, AstraZeneca, Basilea Pharmaceutica, Bayer, Cubist, The Medicines Company, Merck, Ortho-McNeil-Janssen, Paladin Labs, Paratek, Pfizer, Sanofi-Aventis, Sunovion, Tetraphase, Theravance and Zoetis.